When transdermal absorption of a drug is desired, the drug is added to an adhesive matrix and the like and a patch is formed. In recent years, a tape agent more superior in the adhesiveness is more often used than cataplasm containing a large amount of water as a constituent component in the patch. As the adhesive matrix for this tape agent, lipophilic adhesive matrices such as rubber-based, acrylic-based, silicone-based and the like are used.
However, in what is called a “matrix type patch” wherein a drug is directly mixed with an adhesive matrix, a usable preparation sometimes cannot be achieved when a large amount of a drug is contained and the like, since the drug cannot be completely enclosed and exudes out, and adhesiveness decreases.
On the other hand, rivastigmine, i.e., 3-[(1S)-1-(dimethylamino)ethyl]phenyl N-ethyl-N-methylcarbamate, is known as a therapeutic drug for of Alzheimer-type dementia, and the effect thereof is considered to be mainly attributable to the inhibition of acetylcholinesterase and butyrylcholinesterase, which increases intracerebral acetylcholine and activates the intracerebral cholinergic nerve system.
As a patch containing rivastigmine, a transdermal absorption type preparation containing rivastigmine together with an antioxidant in an adhesive substrate composed of polyacrylate or polymethacrylate (patent document 1) is known. However, such preparation has a problem of the aforementioned low adhesiveness and, as a remedy, a transdermal absorption type preparation comprising a backing layer (support), a rivastigmine storage layer containing polymers such as polyacrylate, polymethacrylate, polyisobutylene, polybutene, styrene-isoprene-styrene block copolymer and the like and rivastigmine, and an adhesion layer containing a silicone polymer and a tackifier has been proposed (patent document 2).
“EXELON PATCH”, which is a patch of rivastigmine, has been placed in the market. As mentioned above, it is a transdermal absorption type preparation comprising a rivastigmine storage layer, and an adhesion layer containing a silicone polymer and a tackifier, which has adhesiveness sufficient for use. This patch has many advantages afforded by not being orally ingested, that side effects such as vomiting and the like can be suppressed, a rapid increase in the blood concentration can be suppressed and the like, since rivastigmine does not go into the stomach directly unlike oral drugs.
However, in the domestic clinical tests of EXELON PATCH, an adverse event such as skin reaction and stimulation at the application site was seen in 663 cases (77.3%) out of 858 cases as the safety analysis subjects, and the skin irritation at the application site poses a problem (non-patent document 1). In particular, many of the Alzheimer-type dementia patients are old. The skin of old person is prone to express skin symptoms more often, since it shows low moisturizing function, gets dry and highly likely shows low skin barrier function due to a decreased production quantity of sebum. Therefore, when a patch showing skin irritation is adhered to the aged patients, the possibility is extremely high that some harmful phenomenon occurs on the skin. Examples of other existing preparations composed of a medicament storage layer and an adhesion layer include buprenorphine (analgesis of chronic pain) preparations, and clonidine (therapeutic drug for hypertension) preparations. These two preparations have problems in skin irritation (non-patent documents 2, 3).
On the other hand, as a matrix type transdermal absorption type preparation containing a drug other than rivastigmine, for example, a patch using a rubber-based, acrylate-based or silicone-based adhesive matrix is disclosed as a preparation of tolterodine, an antimuscarinic drug (patent document 3). From the aspect of drug stability, moreover, a patch using a rubber-based adhesive (rubber-based adhesive matrix) showing less interaction with drugs has been proposed (patent documents 4-6). Also in these matrix type preparations, for example, skin irritation at application site has become a problem in Rotigotine (therapeutic drug for Parkinson's disease) preparation and the like (non-patent document 4).